rs3814316

Positions:

• chr1-155177242-G-A
• chr1-155177242-G-C
• chr1-155177242-G-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_025058.5(TRIM46):​c.861G>A​(p.Thr287=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.386 in 1,613,686 control chromosomes in the GnomAD database, including 127,443 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.37 (11219 hom., cov: 32)
  • Exomes 𝑓: 0.39 (116224 hom.)
• Consequence: TRIM46 NM_025058.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.60

Genes affected

TRIM46 (HGNC:19019): (tripartite motif containing 46) This gene encodes a protein of the tripartite motif (TRIM) family. The TRIM motif includes zinc-binding domains, a RING finger region, a B-box motif and a coiled-coil domain. TRIM46 is reported to be involved in the proliferation of multiple types of cancer cells including lung and breast cancer. It has also been shown to control neuronal polarity and axon specification by forming uniform microtubule bundles in the axon. [provided by RefSeq, May 2022]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.7).
• BP7: Synonymous conserved (PhyloP=-1.6 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.75 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRIM46	NM_025058.5	c.861G>A	p.Thr287=	synonymous_variant	5/10	ENST00000334634.9	NP_079334.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRIM46	ENST00000334634.9	c.861G>A	p.Thr287=	synonymous_variant	5/10	1	NM_025058.5	ENSP00000334657	P1

Frequencies

GnomAD3 genomes AF: 0.370 AC: 56193 AN: 151906 Hom.: 11221 Cov.: 32

Gnomad AFR AF: 0.273

Gnomad AMI AF: 0.271

Gnomad AMR AF: 0.486

Gnomad ASJ AF: 0.277

Gnomad EAS AF: 0.771

Gnomad SAS AF: 0.440

Gnomad FIN AF: 0.456

Gnomad MID AF: 0.334

Gnomad NFE AF: 0.361

Gnomad OTH AF: 0.367

GnomAD3 exomes AF: 0.433 AC: 108881 AN: 251372 Hom.: 26141 AF XY: 0.424 AC XY: 57549 AN XY: 135852

Gnomad AFR exome AF: 0.274

Gnomad AMR exome AF: 0.600

Gnomad ASJ exome AF: 0.280

Gnomad EAS exome AF: 0.765

Gnomad SAS exome AF: 0.446

Gnomad FIN exome AF: 0.460

Gnomad NFE exome AF: 0.358

Gnomad OTH exome AF: 0.405

GnomAD4 exome AF: 0.387 AC: 565986 AN: 1461660 Hom.: 116224 Cov.: 47 AF XY: 0.386 AC XY: 280778 AN XY: 727138

Gnomad4 AFR exome AF: 0.263

Gnomad4 AMR exome AF: 0.590

Gnomad4 ASJ exome AF: 0.281

Gnomad4 EAS exome AF: 0.799

Gnomad4 SAS exome AF: 0.440

Gnomad4 FIN exome AF: 0.459

Gnomad4 NFE exome AF: 0.364

Gnomad4 OTH exome AF: 0.382

GnomAD4 genome AF: 0.370 AC: 56200 AN: 152026 Hom.: 11219 Cov.: 32 AF XY: 0.379 AC XY: 28124 AN XY: 74298

Gnomad4 AFR AF: 0.273

Gnomad4 AMR AF: 0.486

Gnomad4 ASJ AF: 0.277

Gnomad4 EAS AF: 0.770

Gnomad4 SAS AF: 0.438

Gnomad4 FIN AF: 0.456

Gnomad4 NFE AF: 0.361

Gnomad4 OTH AF: 0.361

Alfa AF: 0.360 Hom.: 23873

Bravo AF: 0.374

Asia WGS AF: 0.544 AC: 1890 AN: 3478

EpiCase AF: 0.326

EpiControl AF: 0.329

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	0.94
DANN	Benign	0.81

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs3814316; hg19: chr1-155149718; COSMIC: COSV55280507; COSMIC: COSV55280507;